Inhaled nitric oxide (NO) is used to treat elevated pulmonary pressures and pulmonary disorders associated with hypoxemia. This provides hypoxemia relieving and smooth muscle constriction relieving effects, but side effects include inflammation, airway hyperactivity, hemorrhage, and reaction with hemoglobin resulting in interference with its oxygen delivery function. In addition, this impairs renal function and even increases mortality in some subsets. The hypoxemia relieving and smooth muscle constriction relieving effects are due mainly to the vasodilating effect of NO as NO does not mediate production of S-nitrosoglutathione in the lung effectively, as it requires reaction with oxygen for this purpose and this reaction does not proceed readily in the lung. On the other hand, the toxicity of NO is related to reactions with oxygen and reactive oxygen species and is mitigated by airway glutathione and thiols.
Use of nitric oxide-releasing compounds inhaled as solids or liquids in an aerosol (nebulized NO donor compounds) to treat pulmonary vasconstriction and asthma is described in Zapol U.S. Pat. No. 5,823,180. This method while offering certain advantages compared to NO administration has the disadvantages compared to inhaled NO administration that the distribution in the lungs is not matched to perfusion so NO deposits in places where it does not reach the blood and that the method is not readily carried out by an anesthesiologist since anesthesiologists do not normally administer liquids or powders. In addition, the pharmacokinetics of these compounds are different and may reveal systemic effects. Moreover, all the potential toxicities of inhaled NO gas are manifest also with nebulized NO donor compounds as these are converted to NO in the lung. The disadvantages of administering nebulized NO donor are indicated to be meaningful by the fact that inhaled gaseous NO is approved for use over inhaled liquid or inhaled solid NO-releasing compound.
The method of parent patent application Ser. No. 09/390,215 constitutes an improvement over the methods described above which rely on inhaled NO or nebulized NO donor. The method of Ser. No. 09/390,215 comprises delivery into the lungs of a patient with a pulmonary disorder associated with hypoxemia and/or smooth muscle constriction, as a gas, a therapeutically effective amount of a compound having an NO group and having a hypoxemia relieving and smooth muscle constriction relieving effect with said NO group being bound in said compound so that it does not form NO2 or NOx (where NOx means NO, N2O3, N2O4, OONO−, OONO• and any products of their reaction with NO or NO2). This method provides the advantages of administering inhaled NO compared to administering nebulized NO donor, without the toxicities associated with NO inhalation. Other desired effects include reactions with thiols of the red blood cell rather than hemes of hemoglobin so as to improve systemic delivery of oxygen. The preferred treating agent for the method of Ser. No. 09/390,215 is ethyl nitrite.